Melissa Conrad Stöppler, MD

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

Charles Patrick Davis, MD, PhD

Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

What is the alpha-fetoprotein (AFP) blood test?

The most abundant plasma protein found in the human fetus is alpha-fetoprotein (AFP). AFP is a protein normally made by the immature liver cells in the fetus. Healthy, nonpregnant adults have very low levels of AFP in the bloodstream (undetectable to about 10 ng/ml). At birth, infants have relatively high levels of AFP in the blood, which fall to normal low adult levels by the first year of life.

Pregnant women carrying babies with neural tube defects may have high levels of AFP in both the bloodstream, urine, and in the amniotic fluid. A neural tube defect is an abnormal fetal brain or spinal cord that is caused by folic acid deficiency during pregnancy. Examples of these birth defects include spina bifida and anencephaly. Women carrying twins or other multiples may also have elevated levels of AFP due to the presence of multiple fetuses producing AFP. Lower than normal AFP levels in pregnant women are sometimes seen in pregnant women carrying babies with genetic conditions such as Down syndrome.

It is important to note that abnormal levels of AFP in pregnancy do not necessarily mean there is a problem with the baby. If AFP levels are not normal, it means that more tests should be done to determine the cause. The American Pregnancy Association says that all pregnant women should be offered an AFP test sometime between the 15th and 20th week of pregnancy. AFP is typically part of the triple screen or quad screen test (along with human chorionic gonadotropin or HCG, estriol, and inhibin A) used in the second trimester of pregnancy to determine whether additional testing is necessary.

Alpha-fetoprotein is also produced by certain cancers, such as liver or testicular cancer, and is sometimes measured as a tumor marker (see below).

The AFP tumor marker test can be performed on a blood sample, urine sample, or sample of amniotic fluid.. Other names for the test include total AFP, MSAFP (maternal serum AFP), and alpha-fetoprotein-L3 percent (%)

Diagnostic Tests for Liver Cancer

The best way to detect liver cancer is through surveillance ultrasound of the liver done by an oncologist every six months in a patient with a diagnosis of cirrhosis. As with most forms of cancer, it is best to treat the liver cancer as soon as it is detected.

Once a suspicion of liver cancer arises, a physician will order one the following to confirm a diagnosis:

Blood tests: alpha-fetoprotein (AFP), which may be elevated in 70% of patients with liver cancer. AFP levels could be normal in liver cancer. A rising level of AFP is suspicious for liver cancer. The AFP may be elevated with cirrhosis and chronic active hepatitis. Other labs tests include des-gamma-carboxy prothrombin, which can be elevated in most patients with liver cancer.

Imaging studies: Multiphasic helical CT scan and MRI with contrast of the liver are the preferred imaging for detecting the location and extent of blood supply to the cancer. If any imaging study is inconclusive, then an alternative imaging study or follow-up imaging study should be performed to help clarify the diagnosis. Lesions smaller than 1 cm are usually difficult to characterize.

Liver biopsy is performed to sample tissue from the lesion in the liver, which is analyzed by a pathologist to confirm the suspected diagnosis of liver cancer. Liver biopsy is not needed in every case, especially if the imaging study and lab markers are characteristic for liver cancer. Risks of liver biopsy are infection, bleeding, or seeding of the needle track with cancer. Seeding is when cancer cells get on the needle used for a biopsy and spread to other areas touched by the needle. Liver biopsy of suspected liver cancer carries the added risk of seeding the liver biopsy needle track in 1%-3% of cases. If a liver biopsy is inconclusive, then a repeat imaging study is recommended at three- to six-month intervals.

What tests measure AFP?

Several assays (tests) for measuring AFP in the blood (serum) are available to laboratories. Generally, normal levels of AFP are below 10 ng/ml. People with various types of acute and chronic liver diseases without documentable liver cancer can have mild or even moderate elevations of AFP, though usually less than 500 ng/ml.

The blood sample for an AFP test can be obtained in any doctor's office or clinic where blood samples are drawn. The sample is sent to a laboratory for analysis.

What is the sensitivity of AFP for diagnosing liver cancer?

Primary liver cancer, or hepatocellular carcinoma or hepatoma, is more common in some forms of chronic liver disease. As a screening test in patients with chronic hepatitis B and C, or hemochromatosis, AFP has a sensitivity for liver cancer of about 70%. In other words, an elevated AFP blood test is seen in about 70% people with primary liver cancer. That leaves about 30% of patients in these high-risk groups who can have liver cancer but have normal AFP levels. Consequently, the test is not diagnostic but is an indicator of a potential situation. Therefore, a normal AFP does not exclude liver cancer. For example, AFP levels are normal in a patient with fibrolamellar carcinoma, a variant of hepatocellular carcinoma.

As noted above, an abnormal AFP does not mean that an individual has liver cancer. It is important to note, however, that people with cirrhosis (scarring) of the liver and an abnormal AFP, despite having no evidence of liver cancer, still are at very high risk of developing liver cancer. Thus, anyone with cirrhosis and an elevated AFP, particularly with steadily rising blood levels, will either most likely develop liver cancer or actually already have an undiscovered liver cancer.

An AFP greater than 500 ng/ml is very suggestive of liver cancer. In fact, the blood level of AFP loosely relates to (correlates with) the size of the liver cancer.

Finally, in patients with liver cancer and abnormal AFP levels, the AFP may be used as a marker of response to treatment. For example, an elevated AFP is expected to fall to normal in a patient whose liver cancer is successfully removed surgically (resected). If AFP then increases again, liver cancer recurrence is likely.

In certain cancers of the testis as described above, the AFP is measured at diagnosis and followed as a tumor marker in a fashion similar to that described above in people with liver cancer.

AFP is not recommended as a screening tool for detection of cancer in normal, healthy people.

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